Primary objectives of this study are to determine if sodium fluoride (NaF) and calcium therapy for postmenopausal osteoporosis is safe and is efficacious in reducing the incidence of vertebral fractures. Secondary objectives are to assess the relationship between F-induced increases in vertebral bone mineral density (BMD) and fracture incidence; to determine if there is a differential effect of NaF therapy on trabecular and cortical bone and, if so, what is the effect on BMD of the proximal femur; to define the onset and duration of bone response; and to examine variables that may contribute to differences in individual responsiveness. Two hundred (200) otherwise healthy postmenopausal females, ages 50 to 75 yrs, who have osteoporosis and vertebral compression fractures will be equally divided into parallel treatment and control groups by dynamic randomization. The study will be conducted under double-blind conditions. The treatment patients will receive 60 mg daily of NaF in divided doses while the control patients will take matching placebo. Both treatment and control groups will receive 1.0 g daily of calcium as CaCO3 in divided doses. Treatment will be continued for four years. Therapy will be monitored by serum and urine fluoride determinations every 6 mo. Safety will be assessed by continued contact with the patients, by interview every 6 mo., by examination, and by evaluation with standard laboratory tests every year. The number and degree of new vertebral fractures in the treatment group compared with the control group will be assessed by the new and precise (c.v. under 2%) technique of quantitative biplanar roentgenography. Individual responsiveness of therapy will be assessed by serial determinations every 6 mo a) of BMD of the lumbar spine (by dual photon absorptiometry) and b) of the skeletal fraction of serum alkaline phosphatase (by kinetic enzyme assay). BMD of appendicular cortical bone (mid-radius) will be assessed by single photon absorptiometry every 6 mo and BMD of the proximal femur will be assessed by dual photon absorptiometry before, after 2 and after 4 yrs of treatment. Selected subgroups will have metabolic balance studies for F bioavailability and iliac crest biopsy studies for quantitative bone histology and for F content.